O-GlcNAcylation in tumorigenesis and its implications for cancer therapy

J Biol Chem. 2024 Sep;300(9):107709. doi: 10.1016/j.jbc.2024.107709. Epub 2024 Aug 22.

Abstract

O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a dynamic and reversible posttranslational modification that targets serine and threonine residues in a variety of proteins. Uridine diphospho-N-acetylglucosamine, which is synthesized from glucose via the hexosamine biosynthesis pathway, is the major donor of this modification. O-GlcNAc transferase is the sole enzyme that transfers GlcNAc onto protein substrates, while O-GlcNAcase is responsible for removing this modification. O-GlcNAcylation plays an important role in tumorigenesis and progression through the modification of specific protein substrates. In this review, we discuss the tumor-related biological functions of O-GlcNAcylation and summarize the recent progress in the development of pharmaceutical options to manipulate the O-GlcNAcylation of specific proteins as potential anticancer therapies.

Keywords: O-GlcNAcylation; cancer therapy; chemical-induced proximity; tumorigenesis.

Publication types

  • Review

MeSH terms

  • Acetylglucosamine* / metabolism
  • Animals
  • Antineoplastic Agents / therapeutic use
  • Carcinogenesis* / metabolism
  • Glycosylation
  • Humans
  • N-Acetylglucosaminyltransferases* / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Protein Processing, Post-Translational*

Substances

  • N-Acetylglucosaminyltransferases
  • Acetylglucosamine
  • O-GlcNAc transferase
  • Antineoplastic Agents